Journal ArticleDOI
Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial.
Nicola Logallo,Nicola Logallo,Vojtech Novotny,Vojtech Novotny,Jörg Assmus,Christopher Elnan Kvistad,Christopher Elnan Kvistad,Lars Alteheld,Ole Morten Rønning,Ole Morten Rønning,Bente Thommessen,Karl-Friedrich Amthor,Hege Ihle-Hansen,Martin W. Kurz,Martin W. Kurz,Håkon Tobro,Kamaljit Kaur,Magdalena Stankiewicz,Maria Carlsson,Åse Hagen Morsund,Titto T. Idicula,Anne Hege Aamodt,Christian Lund,Halvor Naess,Halvor Naess,Ulrike Waje-Andreassen,Ulrike Waje-Andreassen,Lars Thomassen,Lars Thomassen +28 more
TLDR
Tenecteplase was not superior to alteplase and showed a similar safety profile, and further trials are needed to establish the safety and efficacy in patients with severe stroke and whether tenectePLase is non-inferior to altplase.Abstract:
Summary Background Tenecteplase is a newer thrombolytic agent with some pharmacological advantages over alteplase. Previous phase 2 trials of tenecteplase in acute ischaemic stroke have shown promising results. We aimed to investigate the safety and efficacy of tenecteplase versus alteplase in patients with acute stroke who were eligible for intravenous thrombolysis. Methods This phase 3, randomised, open-label, blinded endpoint, superiority trial was done in 13 stroke units in Norway. We enrolled adults with suspected acute ischaemic stroke who were eligible for thrombolysis and admitted within 4·5 h of symptom onset or within 4·5 h of awakening with symptoms, or who were eligible for bridging therapy before thrombectomy. Patients were randomly assigned (1:1) to receive intravenous tenecteplase 0·4 mg/kg (to a maximum of 40 mg) or alteplase 0·9 mg/kg (to a maximum of 90 mg), via a block randomisation schedule stratified by centre of inclusion. Patients were not informed of treatment allocation; treating physicians were aware of treatment allocation but those assessing the primary and secondary endpoints were not. The primary outcome was excellent functional outcome defined as modified Rankin Scale (mRS) score 0–1 at 3 months. The primary analysis was an unadjusted and non-stratified intention-to-treat analysis with last observation carried forward for imputation of missing data. This study is registered with ClinicalTrials.gov, number NCT01949948. Findings Between Sept 1, 2012, and Sept 30, 2016, 1107 patients met the inclusion criteria and seven patients were excluded because informed consent was withdrawn or eligibility for thrombolytic treatment was reconsidered. 1100 patients were randomly assigned to the tenecteplase (n=549) or alteplase (n=551) groups. The median age of participants was 77 years (IQR 64–79) and the median National Institutes of Health Stroke Scale score at baseline was 4 points (IQR 2–8). A final diagnosis other than ischaemic stroke or transient ischaemic attack was found in 99 (18%) patients in the tenecteplase group and 91 (17%) patients in the alteplase group. The primary outcome was achieved by 354 (64%) patients in the tenecteplase group and 345 (63%) patients in the alteplase group (odds ratio 1·08, 95% CI 0·84–1·38; p=0·52). By 3 months, 29 (5%) patients had died in the tenecteplase group compared with 26 (5%) in the alteplase group. The frequency of serious adverse events was similar between groups (145 [26%] in the tenecteplase group vs 141 [26%] in the alteplase group; p=0·74). Interpretation Tenecteplase was not superior to alteplase and showed a similar safety profile. Most patients enrolled in this study had mild stroke. Further trials are needed to establish the safety and efficacy in patients with severe stroke and whether tenecteplase is non-inferior to alteplase. Funding Research Council of Norway.read more
Citations
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Journal ArticleDOI
Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.
William J. Powers,Alejandro A. Rabinstein,Teri Ackerson,Opeolu Adeoye,Nicholas C. Bambakidis,Kyra J. Becker,José Biller,Michael D. Brown,Bart M. Demaerschalk,Brian L. Hoh,Edward C. Jauch,Chelsea S. Kidwell,Thabele M Leslie-Mazwi,Bruce Ovbiagele,Phillip A. Scott,Kevin N. Sheth,Andrew M. Southerland,Deborah V. Summers,David L. Tirschwell +18 more
TL;DR: These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks.
Journal ArticleDOI
2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association
William J. Powers,Alejandro A. Rabinstein,Teri Ackerson,O.M. Adevoe,Nicholas C. Bambakidis,Kyra J. Becker +5 more
TL;DR: I alteplase treatment should be administered within 3 hours of acute ischemic stroke in appropriate patients and should not be delayed while waiting for hematologic or coagulation testing if there is no reason to suspect an abnormal test.
Journal ArticleDOI
Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke
Bruce C.V. Campbell,Peter Mitchell,Leonid Churilov,Nawaf Yassi,Timothy Kleinig,Richard Dowling,Bernard Yan,Steven Bush,Helen M Dewey,Vincent Thijs,Vincent Thijs,Rebecca Scroop,Marion Simpson,Mark Brooks,Hamed Asadi,Hamed Asadi,Hamed Asadi,Teddy Y. Wu,Teddy Y. Wu,Darshan Shah,Darshan Shah,Tissa Wijeratne,Timothy Ang,Ferdinand Miteff,Christopher R Levi,Edrich Rodrigues,Henry Zhao,Patrick Salvaris,Carlos Garcia-Esperon,Peter L. Bailey,Henry E. Rice,Laetitia de Villiers,Helen Brown,Kendal Redmond,David Leggett,John N. Fink,Wayne Collecutt,Andrew Wong,Claire Muller,Alan Coulthard,Ken Mitchell,John Clouston,Kate Mahady,Deborah Field,Henry Ma,Thanh G. Phan,Winston Chong,Ronil V. Chandra,Lee-Anne Slater,Martin Krause,Timothy Harrington,Timothy Harrington,Kenneth Faulder,Kenneth Faulder,Brendan Steinfort,Brendan Steinfort,Christopher F. Bladin,Christopher F. Bladin,Gagan Sharma,Patricia Desmond,Mark W Parsons,Geoffrey A. Donnan,Stephen M. Davis +62 more
TL;DR: Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset.
Journal ArticleDOI
European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke.
Eivind Berge,William Whiteley,Heinrich J. Audebert,Gian Marco De Marchis,Ana Catarina Fonseca,Chiara Padiglioni,Natalia Pérez de la Ossa,Daniel Strbian,Georgios Tsivgoulis,Georgios Tsivgoulis,Guillaume Turc,Guillaume Turc +11 more
TL;DR: The European Stroke Organisation (ESO) guidelines provide evidence-based recurrence guidelines for patients with acute ischaemic stroke as mentioned in this paper, where intrvenous thrombolysis is the only approved systemic reperfusion treatment.
Journal ArticleDOI
European Stroke Organisation (ESO) – European Society for Minimally Invasive Neurological Therapy (ESMINT) Guidelines on Mechanical Thrombectomy in Acute Ischaemic StrokeEndorsed by Stroke Alliance for Europe (SAFE):
Guillaume Turc,Pervinder Bhogal,Urs Fischer,Pooja Khatri,Kyriakos Lobotesis,Mikael Mazighi,Peter D. Schellinger,Danilo Toni,Joost de Vries,Philip White,Jens Fiehler +10 more
TL;DR: High quality evidence to recommend MT plus best medical management (BMM, including intravenous thrombolysis whenever indicated) to improve functional outcome in patients with LVO-related acute ischaemic stroke within 6 hours after symptom onset is found.
References
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Thrombolysis with Alteplase 3 to 4.5 Hours After Acute Ischemic Stroke
Werner Hacke,Markku Kaste,Erich Bluhmki,Miroslav Brozman,Antoni Dávalos,Donata Guidetti,Vincent Larrue,Kennedy R. Lees,Zakaria Medeghri,Thomas Machnig,Dietmar Schneider,Rüdiger von Kummer,Nils Wahlgren,Danilo Toni +13 more
TL;DR: As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; altePlase was more frequently associated with symptomatic intracranial hemorrhage.
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Intravenous Thrombolysis With Recombinant Tissue Plasminogen Activator for Acute Hemispheric Stroke: The European Cooperative Acute Stroke Study (ECASS)
Werner Hacke,Markku Kaste,Cesare Fieschi,Danilo Toni,Emmanuel Lesaffre,von Kummer R,Gudrun Boysen,Erich Bluhmki,Höxter G,Mahagne Mh +9 more
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Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials
Werner Hacke,Geoffrey A. Donnan,Cesare Fieschi,Markku Kaste,Rüdiger von Kummer,Joseph P. Broderick,Thomas G. Brott,Michael Frankel,James C. Grotta,E. Clarke Haley,Thomas Kwiatkowski,Steven R. Levine,Chris Lewandowski,Mei Lu,Patrick D. Lyden,John R. Marler,Suresh C. Patel,Barbara C. Tilley,Gregory W. Albers,Erich Bluhmki,Manfred Wilhelm,Scott Hamilton,Atlantis Trials Investigators,Ecass Trials Investigators +23 more
TL;DR: The sooner that rt-PA is given to stroke patients, the greater the benefit, especially if started within 90 min, which suggests a potential benefit beyond 3 h, but this potential might come with some risks.
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Guidelines for management of ischaemic stroke and transient ischaemic attack 2008
Peter A. Ringleb,Marie-Germaine Bousser,Gary A. Ford,Philip M.W. Bath,Michael Brainin,Valeria Caso,Álvaro Cervera,Ángel Chamorro,Charlotte Cordonnier,László Csiba,Antoni Dávalos,Hans-Christoph Diener,José M. Ferro,Werner Hacke,Michael G. Hennerici,Markku Kaste,Peter Langhorne,Kennedy R. Lees,Didier Leys,J. Lodder,Hugh S. Markus,Jean-Louis Mas,Heinrich Mattle,Keith W. Muir,Bo Norrving,Victor Obach,Stefano Paolucci,E. Bernd Ringelstein,Peter D. Schellinger,Juhani Sivenius,Skvortsova Vi,Katharina S. Sunnerhagen,Lars Thomassen,Danilo Toni,Rüdiger von Kummer,Nils Wahlgren,Marion F Walker,Joanna M. Wardlaw +37 more
TL;DR: The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation.
Journal ArticleDOI
Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials.
Kennedy R. Lees,Erich Bluhmki,Rüdiger von Kummer,Thomas G. Brott,Danilo Toni,James C. Grotta,Gregory W. Albers,Markku Kaste,John R. Marler,Scott Hamilton,Barbara C. Tilley,Stephen M. Davis,Geoffrey A. Donnan,Werner Hacke +13 more
TL;DR: Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5 h should be taken to shorten delay in initiation of treatment to increase benefit to a maximum.
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